Non-invasive glucose meter

ABSTRACT

An apparatus and method for measuring a concentration of a substance in an eye using a retro-reflected measurement light beam having a first wavelength at which the substance has a non-zero first absorption coefficient and a retro-reflected reference light beam having a second wavelength at which the substance has a second absorption coefficient which is substantially equal to zero. The apparatus further includes a detector positionable to receive the retro-reflected measurement light beam and the retro-reflected reference light beam. The detector is responsive to light having the first wavelength by generating a measurement signal and responsive to light having the second wavelength by generating a reference signal. The apparatus further includes an electrical circuit coupled to the detector. The electrical circuit is responsive to the measurement signal and the reference signal to measure the concentration of the substance in the eye.

CLAIM OF PRIORITY

The present application is a continuation of U.S. patent applicationSer. No. 10/485,876, filed Aug. 12, 2004, which was the national stageof International Application No. PCT/IB02/03774, filed Aug. 1, 2002,which claims priority to U.S. Provisional Application No. 60/309,604,filed Aug. 2, 2001, which is incorporated in its entirety by referenceherein.

BACKGROUND OF THE INVENTION

Numerous systems were suggested in the last decades, to solve theproblem of a Non-Invasive Glucose-Meter.

The main drawback of all those systems was a very poor signal to noiseratio, which required a very heavy computing system, and resulted ininconsistent and unrepeatable results.

SUMMARY OF THE INVENTION

According to one aspect of embodiments of the present invention, amethod determines the concentration of a substance in an eye. The eyehas a cornea, a pupil, an iris, a lens, a liquid, and a retina. Themethod comprises providing a measurement light beam having a firstwavelength at which the substance has a non-zero first absorptioncoefficient. The method further comprises providing a reference lightbeam having a second wavelength at which the substance has a secondabsorption coefficient which is substantially equal to zero. The methodfurther comprises irradiating the retina with the measurement lightbeam, thereby passing the measurement light beam through the cornea, thepupil, the lens, and the liquid. The method further comprisesirradiating the retina with the reference light beam, thereby passingthe reference light beam through the cornea, the pupil, the lens, andthe liquid. The method further comprises reflecting at least a portionof the measurement light beam from the retina and through the liquid,the lens, the pupil, and the cornea, thereby producing a measurementretro-reflected light beam having the first wavelength. The methodfurther comprises reflecting at least a portion of the reference lightbeam from the retina and through the liquid, the lens, the pupil, andthe cornea, thereby producing a reference retro-reflected light beamhaving the second wavelength. The method further comprises providing adetector adapted to generate a measurement signal in response to beingirradiated by light having the first wavelength and to generate areference signal in response to being irradiated by light having thesecond wavelength. The method further comprises irradiating the detectorwith the measurement retro-reflected light beam. The method furthercomprises irradiating the detector with the reference retro-reflectedlight beam. The method further comprises determining the concentrationof the substance in the eye in response to the measurement signal andthe reference signal from the detector.

In another aspect of embodiments of the present invention, an apparatusmeasures a concentration of a substance in an eye having a retina. Theapparatus comprises a measurement light source producing a measurementlight beam having a first wavelength. The substance has a non-zero firstabsorption coefficient for light at the first wavelength. The apparatusfurther comprises a reference light source producing a reference lightbeam having a second wavelength. The substance has a second absorptioncoefficient which is substantially equal to zero for light at the secondwavelength. The apparatus further comprises an optical combinercomprising a dichroic coating layer. The optical combiner ispositionable so that at least a portion of the measurement light beamretro-reflects from the retina and so that at least a portion of thereference light beam retro-reflects from the retina. The apparatusfurther comprises a detector positionable to receive the retro-reflectedmeasurement light beam and the retro-reflected reference light beam. Thedetector is responsive to light having the first wavelength bygenerating a measurement signal and is responsive to light having thesecond wavelength by generating a reference signal. The apparatusfurther comprises an electrical circuit coupled to the detector. Theelectrical circuit is responsive to the measurement signal and thereference signal to measure the concentration of the substance in theeye.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 schematically illustrates the principle of the Electro-Opticconstruction of the Non-Invasive Glucose-Meter in accordance with thepreferred embodiment.

FIG. 2 schematically illustrates the principal of the Electro-Opticconstruction of the Non-Invasive Glucose-Meter in accordance withanother embodiment.

FIG. 3 schematically illustrates the electronic circuit, associated withthe preferred embodiment.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT

It is one objective of embodiments of the present invention to provide aNon-Invasive Glucose-Meter, which has a good signal to noise ratio, thusmaking the measurement consistent, repeatable and reliable.

It is another objective of embodiments of the present invention toprovide such an apparatus for non-invasive glucose measurement, which iseasy and simple to handle by the user, small sized and inexpensive.

It is a further objective of embodiments of the present invention toprovide a Non-Invasive Glucose-Meter, which can be used in variousenvironments, indoors and outdoors.

The objectives of embodiments of this invention can be achieved by usingthe properties of the eye as an optical apparatus. Every opticalapparatus, which is equipped with focusing means and a focal plane,shows the phenomenon of retro-reflection, meaning: reflects back theentering light beam in the same direction it comes from. Embodiments ofthe current invention suggests an Electro-Optical apparatus which usesthe retro-reflection characteristic of the eye in order to determineglucose or other substance concentration in the eye liquid (the vitreousbody).

Certain embodiments of the apparatus has at least two infrared (IR)emitters to emit two different wavelength bands in the direction of theeye. Other embodiments emit the two different wavelength bands by usingone wide band emitter and two narrow band filters. One of the wave bandsis located in a wavelength where the glucose has a high absorptioncoefficient, the other wavelength is used for reference. The use of areference beam compensates for changes of the iris, thus enables the useof the system in various light conditions.

An IR detector is located on the same optical path as the emitter, usinga beam splitter (optical combiner), and thus, the retro-reflected beamfrom the eye returns towards the detector.

The retro-reflected beam passes twice throughout the eye, first throughthe cornea, the eye lens and liquid (vitreous body), then focuses on theretina and subsequently is reflected back through the eye liquid, lensand cornea towards the detector. Due to the long optical path in theeye, the absorption signal, which correlates to the exponential of(α_(λ)x), will be significant even in a low concentration of glucose.

The magnitude of the absorption is proportional to

∫_(λ1)^(λ2)^(α_(λ)x)λ

where x is the length of the optical path through the absorbing mediumand α_(λ) is the absorption coefficient of the glucose at wavelength λ.

By using the retro-reflected light from the eye, which travels through along optical path in the absorbing medium, certain embodiments of thecurrent invention overcome the main drawback of all previous suggestedsystems, and inherently has a good signal to noise ratio. The opticalsystem is quite simple, as described in the preferred embodiment, anddue to the good signal to noise ratio, the processing of the signal isalso simple and inexpensive.

FIG. 1 schematically illustrates the principle of the Electro-Opticalconstruction of the Non-Invasive Glucose-Meter, in accordance with thepreferred embodiment of the invention. An optical combiner 1 is locatedin the center of the system 10. The optical combiner 1 is made of fourlayers: dichroic coating 2, optical glass 25, holographic beam splitter3, and cover glass 21. The dichroic coating 2, applied on one surface ofoptical glass 25, has a center wavelength, corresponding to thewavelength of a light source 4. Light sources 4, 6 and 11 are preferablylaser diodes, or high power infrared light emitting diodes. The dichroiccoating 2 enables 50-60% of the IR beam to pass through, and 40-50% ofthe IR beam to be reflected at a 90° angle towards the eye 13.

On the other surface of the optical glass 25 of the optical combiner 1,there is an holographic beam splitter 3, which has a center wavelength,corresponding to the wavelength of a light source 6. The holographicbeam splitter allows 50-60% of the light beam of the center wavelengthto pass through, and 40-50% of the light beam to be reflected at a 270°angle towards the eye 13. The light beams 18 of the two light sourcesare nearly parallel beams, created by using lenses 5 and 7. The lightbeams 18 are on the same optical path, and have, preferably, a diameterof about 2 mm.

The light beams 18 pass through the cornea 14, enter the iris 22, theeye lens 15 and the eye liquid 16, and focus approximately on the retinaat focal point 23. Part of the beam is reflected from the retina, andsince it comes out of the same focal point 23, it will come out from theeye on the exact optical path of beams 18, but in the oppositedirection, and is described by beam 19, propagating in the direction ofthe optical combiner 1. The beam passes the eye twice, thus the opticalpath in the absorbing medium is long, and the absorption signalcorrelates to the exponential of (α_(λ)x), will be much stronger than inany other suggested method. 50-60% of beam 19 passes through the beamsplitter 3, focuses by means of lens 8 on an IR detector 9. The detectorcan be a silicon detector or PbS detector, or any other kind of IRdetector known in the art.

The system 10 should be, preferably, located at a distance of at least100 mm from the eye, in order to receive mainly the retro-reflected beam19, and not other reflections, from the cornea for example, which areconsidered by the system 10 to be noise.

An alternative construction of the optical combiner 1, can be an opticalcombiner with only a dichroic coating 2. In this method, two lightsources, 4 and 11, change position to emit the light beamsintermittently, by using motor 12. In this variation, dichroic coating 2is a wide band coating for both wavelengths of light sources 4 and 11.

FIG. 2 schematically illustrates the principle of the Electro-Opticalconstruction of the Non-Invasive Glucose-Meter, in accordance withanother embodiment of the present invention. In this embodiment, onlyone wide band light source 4 is used, which can be a miniature lamp. Afilter wheel 7, driven by motor 11, is used to choose the requiredwavelengths. This embodiment is advantageous in case that more than twowavelengths are required in order to analyze glucose or other substancesconcentration.

FIG. 3 schematically illustrates the electronic circuit, associated withthe preferred embodiment of the present invention. A central processingunit (CPU) 1, as Epson 6200, produced by Epson, Japan, controls theoperation of the system.

The circuit is turned on by switch 3, connecting power source 16,preferably a Lithium battery, to the circuit. After a self-check, theCPU displays “Ready” on a display unit 2, such as a liquid crystaldisplay (LCD). To perform a measurement, switch 4 is activated. Then,the CPU starts a measurement procedure. It activates in sequence lightsource 15 through amplifier 10 and light source 14 through amplifier 11,and activates motor 13 through amplifier 12 in the alternativeembodiment. The retro-reflected light signal from the eye, is translatedby IR detector 5 to a voltage signal, which is amplified by amplifier 6,and filtered by filter 7. The analog signal is converted to a digitalform by an Analog to Digital (A/D) converter 8 and is stored by the CPU.After receiving measurement data corresponding to the two wavelengths,the CPU calculates the concentration of the glucose according to theabsorption level, using calibration parameters stored in the E²PROM 9.The result is display on display 2.

The same construction can be used to measure concentrations of othersubstances in the eye liquid, using other wavelengths.

Although the invention has been described in terms of certain preferredembodiments, other embodiments that are apparent to those of ordinaryskill in the art, including embodiments which do not provide all of thefeatures and advantages set forth herein, are also within the scope ofthis invention. Accordingly, the scope of the invention is defined bythe claims that follow.

1. A method of determining the concentration of a substance in an eye,the method comprising: providing a nearly parallel measurement lightbeam having a first wavelength at which the substance has a non-zerofirst absorption coefficient; providing a nearly parallel referencelight beam having a second wavelength at which the substance has asecond absorption coefficient which is substantially equal to zero;irradiating the retina of the eye with the measurement light beam,thereby passing the measurement light beam through the cornea, thepupil, the lens, and the liquid of the eye; irradiating the retina ofthe eye with the reference light beam, thereby passing the referencelight beam through the cornea, the pupil, the lens, and the liquid ofthe eye; reflecting at least a portion of the measurement light beamfrom the retina and through the liquid, the lens, the pupil, and thecornea of the eye, thereby producing a retro-reflected measurement lightbeam having the first wavelength; reflecting at least a portion of thereference light beam from the retina and through the liquid, the lens,the pupil, and the cornea of the eye, thereby producing aretro-reflected reference light beam having the second wavelength;providing a detector responsive to light having the first wavelength andresponsive to light having the second wavelength; irradiating thedetector with the retro-reflected measurement light beam, the detectorgenerating a measurement signal in response thereto; irradiating thedetector with the retro-reflected reference light beam, the detectorgenerating a reference signal in response thereto; and determining theconcentration of the substance in the eye in response to the measurementsignal and the reference signal.
 2. The method of claim 1, wherein thedetector primarily receives the retro-reflected measurement light beamand the retro-reflected reference light beam without receiving otherreflections from the eye.
 3. The method of claim 1, wherein the detectoris located such that the retro-reflected measurement light beam and theretro-reflected reference light beam propagate along an optical path ofat least 100 mm between the eye and the detector.
 4. The method of claim1, wherein the substance comprises glucose.
 5. The method of claim 1,wherein the measurement light beam is provided by a first infrared lightsource and the reference light beam is provided by a second infraredlight source.
 6. The method of claim 1, wherein the measurement lightbeam is focused at a point on the retina.
 7. The method of claim 1,wherein the reference light beam is focused at a point on the retina. 8.An apparatus for measuring a concentration of a substance in an eyehaving a retina, the apparatus comprising: a measurement light sourceproducing a nearly parallel measurement light beam having a firstwavelength, the substance having a non-zero first absorption coefficientfor light at the first wavelength; a reference light source producing anearly parallel reference light beam having a second wavelength, thesubstance having a second absorption coefficient which is substantiallyequal to zero for light at the second wavelength; an optical combinercomprising a dichroic coating layer, the optical combiner positionableso that at least a portion of the measurement light beam retro-reflectsfrom the retina and so that at least a portion of the reference lightbeam retro-reflects from the retina; a detector responsive to lighthaving the first wavelength by generating a measurement signal andresponsive to light having the second wavelength by generating areference signal; and an electrical circuit operatively coupled to thedetector, the electrical circuit responsive to the measurement signaland the reference signal to measure the concentration of the substancein the eye.
 9. The apparatus of claim 8, wherein the detector ispositionable to primarily receive the retro-reflected measurement lightbeam and the retro-reflected reference light beam without receivingother reflections from the eye.
 10. The apparatus of claim 8, whereinthe detector is positionable such that the retro-reflected measurementlight beam and the retro-reflected reference light beam propagate alongan optical path of at least 100 mm between the eye and the detector. 11.The apparatus of claim 8, wherein the substance comprises glucose. 12.The apparatus of claim 8, wherein the measurement light source comprisesa first infrared light source and the reference light beam comprises asecond infrared light source.
 13. A substance-measuring metercomprising: an optical system adapted to irradiate the retina of an eyewith a nearly parallel measurement light beam having a first wavelengthat which a substance has a non-zero first absorption coefficient andadapted to irradiate the retina of the eye with a nearly parallelreference light beam having a second wavelength at which the substancehas a second absorption coefficient which is substantially equal tozero, such that at least a portion of the measurement light beam and atleast a portion of the reference light beam are retro-reflected from theretina, thereby producing a retro-reflected measurement light beamhaving the first wavelength and a retro-reflected reference light beamhaving the second wavelength; a detector adapted to generate ameasurement signal in response to the retro-reflected measurement lightbeam and to generate a reference signal in response to theretro-reflected reference light beam; and an electronic circuitresponsive to the measurement signal and the reference signal bydetermining the concentration of the substance in the eye.
 14. The meterof claim 13, wherein the detector is positionable to primarily receivethe retro-reflected measurement light beam and the retro-reflectedreference light beam without receiving other reflections from the eye.15. The meter of claim 13, wherein the detector is positionable suchthat the retro-reflected measurement light beam and the retro-reflectedreference light beam propagate along an optical path of at least 100 mmbetween the eye and the detector.
 16. A method of using a meter adaptedto measure a concentration of a substance in an eye, the methodcomprising: irradiating the retina of the eye with a nearly parallelfirst light beam having a first wavelength; irradiating the retina ofthe eye with a nearly parallel second light beam having a secondwavelength; receiving at least a portion of the first light beamretro-reflected from the retina; receiving at least a portion of thesecond light beam retro-reflected from the retina; providing a detectoradapted to generate a first signal in response to light having the firstwavelength and to generate a second signal in response to light havingthe second wavelength; irradiating the detector with the receivedportion of the retro-reflected first light beam; irradiating thedetector with the received portion of the retro-reflected second lightbeam; and determining the concentration of the substance in the eye inresponse to signals generated by the detector in response to thereceived portion of the retro-reflected first light beam and in responseto the received portion of the retro-reflected second light beam. 17.The method of claim 16, wherein the detector is primarily irradiated bythe received portion of the retro-reflected first light beam and thereceived portion of the retro-reflected second light beam without beingirradiated by other reflections from the eye.
 18. The method of claim16, wherein the detector is located such that the received portion ofthe retro-reflected measurement light beam and the received portion ofthe retro-reflected reference light beam propagate along an optical pathof at least 100 mm between the eye and the detector.
 19. The method ofclaim 16, wherein the substance comprises glucose.